THE FRICTIONAL COEFFICIENTS IN TI-NB ALLOY

Objectives: To determine the frictional force (FF) of the novel, elastic, bendable titanium-niobium (Ti-Nb) alloy orthodontic wire in stainless steel (SS) brackets and to compare it with those of titanium-nickel (Ti-Ni) and titanium-molybdenum (Ti-Mo) alloy wires. Materials and Methods: Three sizes of Ti-Nb, Ti-Ni, and Ti-Mo alloy wires were ligated with elastic modules to 0.018-inch and 0.022-inch SS brackets. The dynamic FFs between the orthodontic wires and SS brackets were measured at three bracket-wire angles (0゜, 5゜, and 10゜) with an Instron 5567 loading apparatus (Canton, Mass). Results: FFs increased gradually with the angle and wire size. In the 0.018-inch-slot bracket, the dynamic FFs of Ti-Nb and Ti-Ni alloy wires were almost the same, and those of the Ti-Mo alloy wire were significantly greater (P<0.05). FF values were 1.5–2 times greater in the 0.022-inch-slot bracket than in the 0.018-inch-slot bracket, regardless of alloy wire type, and the Ti-Mo alloy wire showed the greatest FF. Scanning electric microscopic images showed that the surface of the Ti-Mo alloy wire was much rougher than that of the Ti-Ni and Ti-Nb alloy wires. Conclusion: These findings demonstrate that the Ti-Nb alloy wire has almost the same frictional resistance as the Ti-Ni alloy wire, although it has a higher elastic modulus

New 60-cm Radio Survey Telescope with the Sideband-Separating SIS Receiver for the 200 GHz Band

We have upgraded the 60-cm radio survey telescope located in Nobeyama, Japan. We developed a new waveguide-type sideband-separating SIS mixer for the telescope, which enables the simultaneous detection of distinct molecular emission lines both in the upper and lower sidebands. Over the RF frequency range of 205-240 GHz, the single-sideband receiver noise temperatures of the new mixer are 40-100 K for the 4.0-8.0 GHz IF frequency band. The image rejection ratios are greater than 10 dB over the same range. For the dual IF signals obtained by the receiver, we have developed two sets of acousto-optical spectrometers and a telescope control system. Using the new telescope system, we successfully detected the 12CO (J=2-1) and 13CO (J=2-1) emission lines simultaneously toward Orion KL in 2005 March. Using the waveguide-type sideband-separating SIS mixer for the 200 GHz band, we have initiated the first simultaneous 12CO (J=2-1) and 13CO (J=2-1) survey of the galactic plane as well as large-scale mapping observations of nearby molecular clouds.Comment: 15 pages, 15 figures, Accepted for publication in PASJ, version with high resolution figures is available via http://www.nro.nao.ac.jp/~nakajima/vst1_2sb.pd

Post-transcriptional regulation of human pregnane X receptor by micro-RNA affects the expression of cytochrome P450 3A4.

金沢大学医薬保健研究域薬学系金沢大学医薬保健研究域薬学系Pregnane X receptor (PXR) is a major transcription factor regulating the inducible expression of a variety of transporters and drug-metabolizing enzymes, including CYP3A4 (cytochrome P450 3A4). We first found that the PXR mRNA level was not correlated with the PXR protein level in a panel of 25 human livers, indicating the involvement of post-transcriptional regulation. Notably, a potential miR-148a recognition element was identified in the 3\u27-untranslated region of human PXR mRNA. We investigated whether PXR might be regulated by miR-148a. A reporter assay revealed that miR-148a could recognize the miR-148a recognition element of PXR mRNA. The PXR protein level was decreased by the overexpression of miR-148a, whereas it was increased by inhibition of miR-148a. The miR-148a-dependent decrease of PXR protein attenuated the induction CYP3A4 mRNA. Furthermore, the translational efficiency of PXR (PXR protein/PXR mRNA ratio) was inversely correlated with the expression levels of miR-148a in a panel of 25 human livers, supporting the miR-148a-dependent regulation of PXR in human livers. Eventually, the PXR protein level was significantly correlated with the CYP3A4 mRNA and protein levels. In conclusion, we found that miR-148a post-transcriptionally regulated human PXR, resulting in the modulation of the inducible and/or constitutive levels of CYP3A4 in human liver. This study will provide new insight into the unsolved mechanism of the large interindividual variability of CYP3A4 expression

Epigenetic regulation of the tissue-specific expression of human UDP-glucuronosyltransferase (UGT) 1A10

Human UDP-glucuronosyltransferase (UGT) 1A10 is not expressed in the liver; however, UGT1A10 is highly expressed in the intestine, contributing to presystemic first-pass metabolism. Earlier studies revealed that hepatocyte nuclear factor (HNF) 1α and Sp1, as well as an intestine-specific transcription factor, caudal type homeobox (Cdx) 2, are involved in the constitutive expression of UGT1A10. However, why UGT1A10 is not expressed in the liver, where HNF1α and Sp1 are abundantly expressed, is unknown. In this study, we sought to elucidate the mechanism, focusing on epigenetic regulation. Bisulfite sequence analysis revealed that the CpG-rich region (-264 to +117) around the UGT1A10 promoter was hypermethylated (89%) in hepatocytes, whereas the UGT1A10 promoter was hypomethylated (11%) in the epithelium of the small intestine. A luciferase assay revealed that the methylation of the UGT1A10 promoter by SssI methylase abrogated transactivity even with overexpressed Cdx2 and HNF1α. The UGT1A10 promoter was highly methylated (86%) in liver-derived HuH-7 cells, where UGT1A10 is not expressed. In contrast, the UGT1A10 promoter was hardly methylated (19%) in colon-derived LS180 cells, where UGT1A10 is expressed. Treatment with 5-aza-2′-deoxycitidine (5-Aza-dC), an inhibitor of DNA methylation, resulted in an increase in UGT1A10 expression only in HuH-7 cells. Moreover, overexpression of HNF1α and Cdx2 further increased UGT1A10 expression only in the presence of 5-Aza-dC. Collectively, we found that DNA hypermethylation would interfere with the binding of HNF1α and Cdx2, resulting in the defective expression of UGT1A10 in human liver. Thus, epigenetic regulation is one of the mechanisms that determine the tissue-specific expression of UGT1A10. © 2013

Special Section on Epigenetic Regulation of Drug Metabolizing Enzymes and Transporters Epigenetic Regulation Is a Crucial Factor in the Repression of UGT1A1 Expression in the Human Kidney

ABSTRACT Human uridine 59-diphospho-glucuronosyltransferase (UGT) 1A1 catalyzes the metabolism of numerous clinically and pharmacologically important compounds, such as bilirubin and SN-38. UGT1A1 is predominantly expressed in the liver and intestine but not in the kidney. The purpose of this study was to uncover the mechanism of the tissue-specific expression of UGT1A1, focusing on its epigenetic regulation. Bisulfite sequence analysis revealed that the CpG-rich region near the UGT1A1 promoter (285 to +40) was hypermethylated (83%) in the kidney, whereas it was hypomethylated (37%) in the liver. A chromatin immunoprecipitation assay demonstrated that histone H3 near the promoter was hypoacetylated in the kidney but hyperacetylated in the liver; this hyperacetylation was accompanied by the recruitment of hepatocyte nuclear factor (HNF) 1a to the promoter. The UGT1A1 promoter in human kidney-derived HK-2 cells that do not express UGT1A1 was fully methylated, but this promoter was relatively unmethylated in human liver-derived HuH-7 cells that express UGT1A1. Treatment with 5-aza-29-deoxycytidine (5-aza-dC), an inhibitor of DNA methylation, resulted in an increase of UGT1A1 mRNA expression in both cell types, but the increase was much larger in HK-2 cells than in HuH-7 cells. The transfection of an HNF1a expression plasmid into the HK-2 cells resulted in an increase of UGT1A1 mRNA only in the presence of 5-aza-dC. In summary, we found that DNA hypermethylation, along with histone hypoacetylation, interferes with the binding of HNF1a, resulting in the defective expression of UGT1A1 in the human kidney. Thus, epigenetic regulation is a crucial determinant of tissue-specific expression of UGT1A1

Terahertz diagnostic systems based on frequency combs without moving parts

We exploit information and communications tech-nologies to build a radio frequency-driven frequency comb spanning several hundred gigahertz. We investigated electro-optic modulators, which can serve as building blocks in frequency combs, terahertz generation and terahertz detection systems. These devices have high potential for applications in robust laser-based diagnostics at electron accelerators. During the last year, we have reduced the pulse length generated by a frequency-comb without moving parts by more than one order of magnitude to less than 150 fs, fitting a Lorentzian-type autocorrelation function

Results of Postoperative Treatments in View of the Surgical Stage of Uterine Endometrial Carcinoma

Background : The indications for and the optimal mode of adjuvant therapy in surgically operated endometrial cancer patients have not yet been established. We studied the indications for the postoperative treatment of endometrial carcinoma patients based on their surgical stages (FIGO, 1988) . Methods : We retrospectively restaged the cases of 178 endometrial carcinoma patients who underwent hysterectomy with pelvic lymphadenectomy between 1965 and 1992 and who were followed-up longer than 3 years. The patients were subdivided into low- and high-risk groups, and we investigated the relation between their postoperative treatment and recurrence rates. Postoperative treatment was divided into the three groups of no/incomplete, external whole-pelvic irradiation (EWPI) and chemotherapy. Results : The 79 patients in Stage Ia or Ib had no/incomplete postoperative treatment, but only 1 (1.3%) had a recurrence. Four Stage IIa patients had no recurrence and all 3 low-risk patients had no postoperative treatment. Of the 5 Stage IIb, low-risk patients, 1 of the no postoperativetreatment group had a recurrence. The recurrence rate among the Stage IIb patients of the high-risk group was 40% (2/5) in the incomplete postoperative treatment group. The six Stage IIIa patients with EWPI. had no recurrence. In contrast, 14 of the 15 Stage IIIb and IIIc patients underwent postoperative EWPI, and 11 of them (78.6%) had a recurrence including 8 (81.8%) with a recurrence in distant regions. Conclusion : Postoperative treatment may be well omitted for many patients at Stage Ia or Ib and the low-risk group at Stage IIa based on surgical staging criteria. Patients in other surgical stages seemed to require to identify best postoperative treatment , but further randomized prospective studies will be required to identift the best mode of treatment

Characterization of human UGT2A3 expression using a prepared specific antibody against UGT2A3

UDP-Glucuronosyltransferase (UGT) 2A3 belongs to a UGT superfamily of phase II drug-metabolizing enzymes that catalyzes the glucuronidation of many endobiotics and xenobiotics. Previous studies have demonstrated that UGT2A3 is expressed in the human liver, small intestine, and kidney at the mRNA level; however, its protein expression has not been determined. Evaluation of the protein expression of UGT2A3 would be useful to determine its role at the tissue level. In this study, we prepared a specific antibody against human UGT2A3 and evaluated the relative expression of UGT2A3 in the human liver, small intestine, and kidney. Western blot analysis indicated that this antibody is specific to UGT2A3 because it did not cross-react with other human UGT isoforms or rodent UGTs. UGT2A3 expression in the human small intestine was higher than that in the liver and kidney. Via treatment with endoglycosidase, it was clearly demonstrated that UGT2A3 was N-glycosylated. UGT2A3 protein levels were significantly correlated with UGT2A3 mRNA levels in a panel of 28 human liver samples (r = 0.64, p <0.001). In conclusion, we successfully prepared a specific antibody against UGT2A3. This antibody would be useful to evaluate the physiological, pharmacological, and toxicological roles of UGT2A3 in human tissues. (C) 2019 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.Peer reviewe

The menace of obesity to depression and anxiety prevalence

The incidence of depression and anxiety is amplified by obesity. Mounting evidence reveals that the psychiatric consequences of obesity stem from poor diet, inactivity, and visceral adipose accumulation. Resulting metabolic and vascular dysfunction, including inflammation, insulin and leptin resistance, and hypertension, have emerged as key risks to depression and anxiety development. Recent research advancements are exposing the important contribution of these different corollaries of obesity and their impact on neuroimmune status and the neural circuits controlling mood and emotional states. Along these lines, this review connects the clinical manifestations of depression and anxiety in obesity to our current understanding of the origins and biology of immunometabolic threats to central nervous system function and behavior. © 2021 The Author